Exploring the Potential of Xanthatin from Cuban Xanthium strumarium: Isolation, Characterization, and Biological Evaluation

Berenguer A; Osoria L; Gonzalez Suarez N; Manso A; Salomon S; Padron Yaquis AS; Annabi B; Piloto-Ferrer J*

Berenguer A, Osoria L, Gonzalez Suarez N, Manso A, Salomon S, Padron Yaquis AS, Annabi B and Piloto-Ferrer J*

Volume5-Issue9
Dates: Received: 2024-09-12 | Accepted: 2024-09-20 | Published: 2024-09-20
Pages: 1176-1186

Abstract

Xanthatin possesses anticancer activities through its effect on cancer cell proliferation, apoptosis and metastasis In vitro and In vivo. Here, we described the isolation procedure, characterization and In vitro biological evaluation of the active metabolite xanthatin from Xanthium strumarium grown in Cuba. From the aerial parts of X. strumarium, 995 mg of xanthatin was isolated in the form of prismatic crystals with a yield of 0.07%. The crystals obtained were characterized by HPLC-UV and spectroscopic techniques including UV, IR, and one- and two-dimensional NMR. The signals observed in the spectra obtained confirmed the structure of xanthatin, especially the two-dimensional NMR spectra. The absence of the coupling signal between the H-8 and H-7 protons in the NOESY spectrum allowed us to identify that the fusion of the 7-membered ring and the lactone ring occurs with trans stereochemistry. The isolated xanthatin undergoes a phase transition at 114.30 ± 0.03°C, a value in good agreement with the melting point reported for commercial xanthatin. Biological evaluation showed that xanthatin inhibited the proliferation of HT-29 colorectal cancer cells and HeLa cervical cancer cells, with the greatest inhibitory potential against colorectal cancer. The molecule can also inhibit cell cycle progression by inducing cell cycle arrest at the G2/M phase in HeLa and HT-29 cells, with the greatest effect in HT-29. In conclusion, this study demonstrates promising therapeutic effects of xanthatin from X. strumarium grown in Cuba against colorectal and cervical cancer cell lines, and provides new insights into its potential and effective antitumor properties.

FullText HTML FullText PDF DOI: 10.37871/jbres2006

Certificate of Publication

Copyright

How to cite this article

Berenguer A, Osoria L, González Suarez N, Manso A, Salomón S, Padrón Yaquis AS, Annabi B, Piloto-Ferrer J. Exploring the Potential of Xanthatin from Cuban Xanthium strumarium: Isolation, Characterization, and Biological Evaluation. J Biomed Res Environ Sci. 2024 Sept 20; 5(9): 1176-1186. doi: 10.37871/jbres2006, Article ID: JBRES2006, Available at: https://www.jelsciences. com/articles/jbres2006.pdf

Subject area(s)

Pharmacology

References

Rajabi S, Maresca M, Yumashev AV, Choopani R, Hajimehdipoor H. The Most Competent Plant-Derived Natural Products for Targeting Apoptosis in Cancer Therapy. Biomolecules. 2021 Apr 3;11(4):534. doi: 10.3390/biom11040534. PMID: 33916780; PMCID: PMC8066452.
Piloto-Ferrer J, Stoiber T, Parra AV, Hurtado VY, Ferrada CR, Sanabria MLG, Sánchez-Lamar A. Search of new antimitotics compounds from the Cuban flora. Boletin Latinoamericano y del Caribe de Plantas Medicinales y Aromaticas. 2011;10(1):75-82.
Piloto-Ferrer J, Sánchez-Lamar Á, Francisco M, González ML, Merino N, Aparicio G, Pérez C, Rodeiro I, Lopes MTP. Xanthium strumarium´s xanthatins induces mitotic arrest and apoptosis in CT26WT colon carcinoma cells. Phytomedicine. 2019 Apr;57:236-244. doi: 10.1016/j.phymed.2018.12.019. Epub 2018 Dec 17. PMID: 30797985.
Sánchez-Lamar A, Piloto-Ferrer J, Fiore M, Stano P, Cozzi R, Tofani D, Cundari E, Francisco M, Romero A, González ML, Degrassi F. Xanthium strumarium extract inhibits mammalian cell proliferation through mitotic spindle disruption mediated by xanthatin. J Ethnopharmacol. 2016 Dec 24;194:781-788. doi: 10.1016/j.jep.2016.11.006. Epub 2016 Nov 11. PMID: 27840259.
Kamboj A, Saluja AK. Phytopharmacological review of Xanthium strumarium L.(Cocklebur). International Journal of Green Pharmacy. 2010:4(3).
Fan W, Fan L, Peng C, Zhang Q, Wang L, Li L, Wang J, Zhang D, Peng W, Wu C. Traditional Uses, Botany, Phytochemistry, Pharmacology, Pharmacokinetics and Toxicology of Xanthium strumarium L.: A Review. Molecules. 2019 Jan 19;24(2):359. doi: 10.3390/molecules24020359. PMID: 30669496; PMCID: PMC6359306.
Romero M, Zanuy M, Rosell E, Cascante M, Piulats J, Font-Bardia M, Balzarini J, De Clerq E, Pujol MD. Optimization of xanthatin extraction from Xanthium spinosum L. and its cytotoxic, anti-angiogenesis and antiviral properties. Eur J Med Chem. 2015 Jan 27;90:491-6. doi: 10.1016/j.ejmech.2014.11.060. Epub 2014 Dec 1. PMID: 25481815; PMCID: PMC7115430.
Ruiz-Reyes E, Suarez M. Lactonas sesquiterpénicas. Diversidad estructural y sus actividades biológicas. Revista CENIC Ciencias Biológicas. 2015;46(1):9-24.
Zaki M, Loubidi M, Bilgiç T, Birim D, Akssira M, Dagcı T, Berteina-Raboin S, Saso L, Khouili M, Armagan G. Design, Synthesis, and Biological Evaluation of Novel Tomentosin Derivatives in NMDA-Induced Excitotoxicity. Pharmaceuticals (Basel). 2022 Mar 30;15(4):421. doi: 10.3390/ph15040421. PMID: 35455419; PMCID: PMC9027110..
Bosco A, Golsteyn RM. Emerging Anti-Mitotic Activities and Other Bioactivities of Sesquiterpene Compounds upon Human Cells. Molecules. 2017 Mar 13;22(3):459. doi: 10.3390/molecules22030459. PMID: 28335397; PMCID: PMC6155193.
Geng YD, Zhang L, Wang GY, Feng XJ, Chen ZL, Jiang L, Shen AZ. Xanthatin mediates G2/M cell cycle arrest, autophagy and apoptosis via ROS/XIAP signaling in human colon cancer cells. Nat Prod Res. 2020 Sep;34(18):2616-2620. doi: 10.1080/14786419.2018.1544976. Epub 2018 Dec 27. PMID: 30587055.
Zhou Y, Zhu X, Lin S, Zhu C, Wu L, Chen R, Chen Z, Li W. A Novel Nanoparticle Preparation to Enhance the Gastric Adhesion and Bioavailability of Xanthatin. Int J Nanomedicine. 2020 Jul 14;15:5073-5082. doi: 10.2147/IJN.S252049. PMID: 32764937; PMCID: PMC7368565.
Tao L, Cao Y, Wei Z, Jia Q, Yu S, Zhong J, Wang A, Woodgett JR, Lu Y. Xanthatin triggers Chk1-mediated DNA damage response and destabilizes Cdc25C via lysosomal degradation in lung cancer cells. Toxicol Appl Pharmacol. 2017 Dec 15;337:85-94. doi: 10.1016/j.taap.2017.10.015. Epub 2017 Oct 23. PMID: 29074359.
Takeda S, Nishimura H, Koyachi K, Matsumoto K, Yoshida K, Okamoto Y, Amamoto T, Shindo M, Aramaki H. (-)-Xanthatin induces the prolonged expression of c-Fos through an N-acetyl-L-cysteine (NAC)-sensitive mechanism in human breast cancer MDA-MB-231 cells. J Toxicol Sci. 2013;38(4):547-57. doi: 10.2131/jts.38.547. PMID: 23824011.
Piloto-Ferrer J, Sanchez-Lamar A. Blancos mitóticos de drogas naturales y nuevas estrategias para la terapia anti-cáncer. Revista Cubana de Ciencias Biológicas. 2015:4(2).
Fernandez MF, Piloto-Ferrer J, Annabi B. Targeting of cancer cell drug resistance phenotype and metastasis with xanthium strumarium L. In: Trends in Pharmaceutical Research and Development. Book Publisher International; 2020:59-78. doi: 10.9734/bpi/tprd/v3.
Francisco Fernandez M, Charfi C, Piloto-Ferrer J, Lidia González M, Lamy S, Annabi B. Targeting Ovarian Cancer Cell Cytotoxic Drug Resistance Phenotype with Xanthium strumarium L. Extract. Evid Based Complement Alternat Med. 2019 Nov 15;2019:6073019. doi: 10.1155/2019/6073019. PMID: 31827554; PMCID: PMC6885198.
Ullah R, Nasrullah Khan, Nina Hewitt, Kishwar Ali, David Aaron Jones, Muhammad Ezaz Hasan Khan. Invasive species as rivals: Invasive potential and distribution pattern of xanthium strumarium sustainability. 2022;14(12):7141. doi: 10.3390/su14127141.
Ramírez-Erosa I, Huang Y, Hickie RA, Sutherland RG, Barl B. Xanthatin and xanthinosin from the burs of Xanthium strumarium L. as potential anticancer agents. Can J Physiol Pharmacol. 2007 Nov;85(11):1160-72. doi: 10.1139/Y07-104. PMID: 18066118.
Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods. 1983 Dec 16;65(1-2):55-63. doi: 10.1016/0022-1759(83)90303-4. PMID: 6606682.
Zhi XY, Song LL, Liang J, Wei SQ, Li Y, Zhang Y, Hao XJ, Cao H, Yang C. Synthesis and in vitro antifungal activity of new Michael-type amino derivatives of xanthatin, a natural sesquiterpene lactone from Xanthium strumarium L. Bioorg Med Chem Lett. 2022 Jan 1;55:128481. doi: 10.1016/j.bmcl.2021.128481. Epub 2021 Nov 28. PMID: 34852242.
Li L, Liu P, Xie Y, Liu Y, Chen Z, Geng Y, Zhang L. Xanthatin inhibits human colon cancer cells progression via mTOR signaling mediated energy metabolism alteration. Drug Dev Res. 2022 Feb;83(1):119-130. doi: 10.1002/ddr.21850. Epub 2021 Jun 28. PMID: 34180556.
Xie Y, Zhu X, Liu P, Liu Y, Geng Y, Zhang L. Xanthatin inhibits non-small cell lung cancer proliferation by breaking the redox balance. Drug Dev Res. 2022 Aug;83(5):1176-1189. doi: 10.1002/ddr.21941. Epub 2022 Apr 24. PMID: 35466412.